section name header

Basics ⬇

Basics

Definition

Myxomatous mitral valve disease is characterized by progressive myxomatous degeneration, which refers to a characteristic pathologic weakening and disturbance in the organization of the connective tissue of the AV valve (mitral and tricuspid) apparatus.

Pathophysiology

  • Lesions characterized by pathologic weakening and disorganization of valvular connective tissue, in which the spongiosa component is unusually prominent with accumulation of mucopolysaccharides and glycosaminoglycans.
  • The valve leaflets become thickened and elongated with disease progression.
  • Degenerative changes in the chordae tendineae lead to thickening and elongation of these structures; thereby contributing to systolic atrial displacement of the valve leaflets (valve prolapse).
  • With progression, the valve lesions cause insufficient coaptation of the leaflets during systole, leading to backward regurgitation of blood from the ventricle into the atrium.
  • Severity and progression of AV valve regurgitation depends on severity and progression of valve lesions (leaflets and/or tendinous chords).
  • Compensatory mechanisms include cardiac dilatation and eccentric hypertrophy, increased force of contraction, increased heart rate, increased pulmonary lymphatic drainage (left-sided AV valve regurgitation), fluid retention, and neurohormonal modulation of cardiovascular function.
  • With progression, the valvular regurgitation can no longer be compensated, leading to reduced cardiac output and increased venous pressures (leading to pulmonary edema if left-sided congestive heart failure [CHF] and to ascites if right-sided). With atrial tear, acute cardiac tamponade may result.

Systems Affected

  • Cardiovascular-both AV valves are commonly affected, but semilunar valves less commonly affected.
  • Hepatobiliary-passive congestion.
  • Renal/Urologic-prerenal azotemia.
  • Respiratory-if edema and/or pulmonary hypertension develops.

Genetics

Etiology currently unknown, but the current leading scientific hypothesis is that a genetically determined dystrophic process initiates the valve degeneration. The age at which the disease develops is inherited as a polygenetic threshold trait (i.e., multiple genes influence the trait and a certain threshold has to be reached before the disease develops).

Incidence/Prevalence

The most common cardiac disease in dogs. The prevalence is strongly influenced by age. It is uncommon in young individuals but common in old dogs. The prevalence reaches >90% in some affected dog breeds >10 years.

Signalment

Species

Mainly dogs. Extremely rare in cats.

Breed Predilections

Typically small breeds (<20 kg but may be encountered in larger dogs), such as Cavalier King Charles spaniels, Chihuahuas, Miniature schnauzers, Maltese, Pomeranians, Cocker spaniels, Pekingese, Poodles, and others.

Mean Age and Range

Murmur may be detected from 2 years of age with a peak incidence at 6–8 years in affected breeds, such as Cavalier King Charles spaniels. Onset of CHF from 8–12 years.

Predominant Sex

Males develop the disease at a younger age than females, which means a higher prevalence at a given age in males.

Signs

Signs depend on the stage of disease. The descriptions here align with the grading system described in the ACVIM consensus statement on myxomatous mitral valve disease.

Clinically Healthy Patients but Belonging to a Risk Group (ACVIM Stage A)

No abnormal findings

Patients Without Overt Clinical Signs (ACVIM Stage B)

  • Systolic click (early stage).
  • Systolic murmur best heard over the mitral or tricuspid areas.
  • Murmurs may range from being of soft, low intensity to loud holosystolic. With progression, the murmur typically gets louder and radiates more widely.
  • Initially patients have no obvious radiographic or echocardiographic changes in cardiac chamber size (ACVIM stage B1). As the disease progresses, evidence of cardiomegaly will be seen (ACVIM stage B2), often before obvious clinical signs of heart failure are recognized.

Patients with Overt Clinical Signs or Stabilized by CHF Therapy (ACVIM stages C and D)

  • Usually loud heart murmur.
  • Tachycardia and loss of respiratory sinus arrhythmia.
  • Arrhythmia and pulse deficit may be present, most commonly supraventricular premature beats or atrial fibrillation.
  • Weak femoral pulse, prolonged capillary refill time and pale mucous membranes in case of low output failure.
  • Tachypnea/dyspnea/orthopnea in case of decompensated CHF.
  • Respiratory crackles/rales in case of decompensated CHF.
  • Pink froth, i.e., pulmonary edema may be evident in the nostrils and oropharynx in cases with severe decompensated CHF.
  • Ascites if right-sided CHF.
  • Diagnostic imaging invariably shows left atrial (LA) and ventricular (LV) dilatation and eccentric hypertrophy, sometimes bilateral enlargement, and evidence of pulmonary congestion/edema.

Causes

Primary (inciting) factor unknown, but the disease is influenced by genetic factors in affected breeds.

Risk Factors

  • Breed
  • Sex (males have an earlier onset)

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Dilated cardiomyopathy
  • Congenital heart disease
  • Bacterial endocarditis
  • Chronic airway or interstitial lung disease
  • Pneumonia
  • Pulmonary embolism
  • Pulmonary neoplasia
  • Heartworm disease

CBC/Biochemistry/Urinalysis

  • CBC/Biochemistry usually unremarkable unless severe disease and ongoing CHF therapy
  • Prerenal azotemia secondary to impaired renal perfusion; urinary specific gravity is high unless complicated by underlying renal disease or previous diuretic administration.
  • High liver enzyme activity in many patients with right-sided CHF.

Other Laboratory Tests

  • Natriuretic peptides-concentrations are often unremarkable unless moderate to severe disease.
  • Serum troponin I-concentrations unremarkable unless severe disease.

Imaging

Radiographic Findings

  • Heart size ranges from normal to left-sided or generalized cardiomegaly.
  • LA enlargement is usually the earliest finding.
  • Left-sided CHF-pulmonary congestion; increased interstitial pattern ± air bronchograms; initially, congestion and edema are perihilar, with all lung fields eventually showing changes.

Echocardiographic Findings

  • Thickening and distortion of the AV valve leaflets.
  • Elongation and rupture of the chordae tendineae, causing mitral valve prolapse.
  • Atrial dilatation (uni- or bilaterally).
  • The LV might be distended and is hyperdynamic if the regurgitant flow is high and myocardial function intact; as the ventricle becomes more grossly distended, it may become normo- or, less commonly, hypodynamic because of myocardial failure.
  • Pericardial effusion (usually mild) is rarely seen.
  • Doppler studies document a jet of regurgitation into the left atrium.
  • Doppler evaluation for the presence of pulmonary hypertension should be routinely performed.

Diagnostic Procedures

  • Systemic blood pressure should be monitored in patients with severe disease or receiving diuretics to check for hypotension. Hypertension is not common.
  • Arterial/venous blood gases can be used to quantify hypoxemia and monitor treatment response.
  • Abdominocentesis/Pleurocentesis-a modified transudate is characteristic of CHF.

Electrocardiographic Findings

  • Sinus tachycardia is common in patients with CHF.
  • May show evidence of LA enlargement (P mitrale) or LV enlargement (tall and wide R waves).
  • Supraventricular, most commonly atrial fibrillation, or ventricular arrhythmias may develop in severe disease.

Pathologic Findings

  • Gross valvular changes range from only a few discrete nodules at the line of closure to gross distortion of the valve by gray-white nodules and plaques causing contraction of the cusps and rolling of the free edge; the chordae are irregularly thickened, with regions of tapering and rupture.
  • Mild disease-normal cardiac size. More progressed cases-LA and LV dilation. Degree of right-sided dilatation variable.
  • The degree of LV hypertrophy may be apparent only on weighing the heart.
  • Jet lesions-irregular thickening and opacity of the atrial endocardium.
  • Recent and healed LA splits or tears in some patients.
  • Small thrombi in the LA are rarely seen.

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

Treat patients that need oxygen support as inpatients; if stable, patients may be managed at home.

Nursing Care

Oxygen therapy as needed for hypoxemia.

Activity

  • Absolute exercise restriction for symptomatic patients.
  • Stable patients receiving medical treatment-avoid strenuous exercise.

Diet

  • Prevent cardiac cachexia by ensuring adequate calorie intake.
  • Avoid food with high sodium content.

Client Education

  • Discuss the progressive nature of the disease.
  • Mild disease severity is suggestive of a long period without clinical signs; moderate to severe indicates a shorter period.
  • If the client is a breeder, inform him/her about the genetics of the disease and impact of the finding on future breeding.
  • Appropriate level of exercise, but at the same time maintain quality of life.
  • Common signs of CHF listed above.
  • How to medicate (if indicated)-consistent dosing and that doses of diuretics should be adjusted in collaboration with the veterinarian.
  • Possible adverse side reactions of medications.
  • How to monitor resting/sleeping respiratory rates at home, and at which rate new contact with the clinician should be initiated.
  • Diet (if indicated)-emphasize the importance of avoiding cardiac cachexia by paying close attention to appetite and using an appropriate diet.

Surgical Considerations

Surgical valve replacement and purse-string suture techniques to reduce the area of the mitral valve orifice have been used; experience with these techniques and access usually limited.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

Recommended treatment depends on the stage of the disease; these recommendations follow the guidelines set by the consensus statement developed by the ACVIM.

Patients Without Overt Clinical Signs (ACVIM Stage B)

  • If no cardiac enlargement, no treatment is currently recommended.
  • Administering ACE inhibitors to Stage B2 patients is of unproven efficacy (despite two clinical trials). Administration of pimobendan to Stage B2 patients is of unknown value at this time.

Patients Showing Overt Clinical Signs (ACVIM stage C and D)

Signs of Acute CHF (Often Treated as Inpatient)

  • Furosemide IV, SC, IM, or PO. Dose is dependent on severity of CHF.
    • Mild to moderate CHF: 2–4 mg/kg q8–24h.
    • Severe or fulminant CHF: 4–8 mg/kg q2–6h, preferably IV, IM, or SC.
    • Monitor outcome of treatment by respiratory rate and general clinical status. Dosages can often be reduced when the patient has stabilized.
  • Oxygen supplementation and cage rest to patients with significant dyspnea. 40% in O2 cage (can go as high as 100%) up to 24 hours; nasal O2 in may be used in large-breed dogs, 50–100 mL/kg/minute through humidifier.
  • Pimobendan at 0.25 mg/kg q12h PO.
  • Additional options in cases with severe fulminant CHF:
    • Nitroglycerin: ointment (one-fourth inch/5 kg up to 2 inches percutaneously) or injectable (1–5 µg/kg/minute CRI).
    • Arterial vasodilator to decrease afterload rapidly, such as hydralazine at 0.5 mg/kg q12h titrated up to 2 mg/kg if necessary), or sodium nitroprusside at 1–10 µg/kg/minute. Both drugs require blood pressure monitoring and should be considered only in hospitalized dogs when monitored by a specialist.
    • Dobutamine (dogs, 1–10 µg/kg/minute; cats, 1–5 µg/kg/minute).
    • Dopamine (1–10 µg/kg/minute).
  • Antiarrhythmics-as needed.
  • Severe ascites may require abdominal paracentesis.

Chronic CHF (Typically Treated as Outpatient)

  • Exact composition of medical therapy depends on disease severity and clinical signs. All dogs with CHF require life-long treatment with a diuretic, such as furosemide.
    • Mild to moderate CHF: 1 mg/kg q24h to 3–4 mg/kg q8h PO.
    • Moderate to severe CHF: 2–3 mg/kg q12h or higher.
  • Pimobendan at 0.25 mg/kg q12h PO.
  • ACEI (i.e., enalapril, benazepril, ramipril). Dose and dose interval dependent on ACE inhibitor used (enalapril [0.5 mg/kg q12–24h], benazepril [0.25–0.5 mg/kg q24h]).
  • Spironolactone at 2 mg/kg q12–24h PO and/or hydrochlorothiazide at 2–4 mg/kg q12h PO.
  • Digoxin at 0.22 mg/m2 q12h PO, or lower.
  • Adequate antiarrhythmic treatment if significant arrhythmia is present.
  • Sildenafil at 0.5–2 mg/kg in case of pulmonary hypertension.

Precautions

  • Use digoxin, diuretics, and ACE inhibitors with caution in patients with renal disease.
  • Nitrate tolerance may develop if appropriate 12-hour nitrate-free intervals are omitted from the dosing schedule.
  • Beta-blockers are negative inotropes and may have an acute adverse effect on myocardial function and clinical status.

Possible Interactions

  • Furosemide potentiates the effects of an ACE-inhibitor, spironolactone, or a thiazide.
  • Nonsteroidal anti-inflammatory drugs should be used with caution in patients receiving furosemide and ACEI.

Alternative Drug(s)

  • Diuretics-add thiazide and/or potassium sparing diuretic (e.g., spironolactone) in refractory animals.
  • Torsemide and bumetanide are alternatives to furosemide.
  • Vasodilators-isosorbide dinitrate can be used in place of nitroglycerin ointment in patients requiring long-term nitrate administration.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

  • Frequency of reexaminations depends on severity of myxomatous valve disease and severity of CHF (if present).
  • Dogs without signs of CHF.
    • Slight to moderate disease severity: Perform echocardiography when a murmur is first detected and every 6-12 months thereafter to document progressive cardiomegaly. A baseline radiograph may be useful.
    • Moderate to severe disease severity may require more frequent monitoring.
  • Dogs with signs of CHF:
    • Once acute CHF has been successfully treated, dogs can be treated at home.
    • Reexamination after 1 to 2 weeks of therapy (check for signs of decompensated CHF, dehydration, electrolyte imbalance, renal dysfunction, and presence of a complication). Moderate to severe disease severity may require more frequent monitoring.
    • Thereafter once every 3-6 months if the patient is stable on the medication. More severe cases may require more frequent monitoring.
  • Monitor BUN and creatinine when diuretics and ACE inhibitors are used in combination. Monitor potassium levels, especially when combinations of spironolactone, ACE inhibitors and digoxin are used.

Possible Complications

  • Asymptomatic patients may develop CHF
  • Recurrent CHF in patients stabilized by medical therapy
  • Pulmonary hypertension
  • Biventricular CHF in patients with initial left-sided CHF
  • Mild pleural and/or pericardial effusion
  • Arrhythmia, most commonly atrial fibrillation
  • Rupture of first-order tendinous chord(s), leading to a flail valve leaflet
  • Atrial tear leading to acquired atrial septal defect or cardiac tamponade
  • Formation of intracardiac thrombus and/or myocardial infarction.

Expected Course and Prognosis

The lesions on the AV valves are progressive in nature and myocardial function may worsen, necessitating increasing drug dosages; long-term prognosis depends on response to treatment and stage of heart failure.

Miscellaneous ⬆

Miscellaneous

Synonyms

  • Chronic valvular disease (CVD)
  • Chronic mitral valve disease
  • Degenerative valvular disease
  • Degenerative mitral valve disease (DMVD)
  • Myxomatous mitral valve disease (MMVD)
  • Endocardiosis

Abbreviations

  • ACE = angiotensin converting enzyme
  • AV = atrioventricular
  • CHF = congestive heart failure
  • LA = left atrium
  • LV = left ventricle
  • MAVD = myxomatous mitral valve disease

Authors Ingrid Ljungvall and Jens Häggström

Consulting Editors Larry P. Tilley and Francis W.K. Smith, Jr.

Client Education Handout Available Online

Suggested Reading

Atkins C, Bonagura JD, Ettinger SJ, et al. Guidelines for the diagnosis and treatment of canine chronic valvular heart disease. J Vet Intern Med 2009, 23:1142–1150.

Höijer-Olsen L, Häggström J, Pedersen HD. Acquired valvular heart disease. In: Ettinger SJ, Feldman E, (eds). Textbook of Veterinary Internal Medicine: Diseases of Dogs and Cats. 7th ed. Philadelphia: WB Saunders, 2010, pp 1209–1319.

Borgarelli M, Häggström J. Canine degenerative myxomatous mitral valve disease: natural history, clinical presentation and therapy. Vet Clin North Am Small Anim Pract 2010, 40:651–663.